The aims of this proposal concerning Marek's disease of the chicken are two-fold. First, we wish to further define the pathogenesis of the demyelinating neuropathy which occurs in the "classic disease". We recently showed that birds with this syndrome possess specific humoral and cellular immune responses to peripheral nerve and myelin. Here, we propose to investigate pathologic effects induced by the immune cells and serum. In the second part of the application, we propose to identify and characterize the viral-associated polypeptides induced by Marek's viruses during lytic and neoplastic interactions of chicken tissues. Quantitative differences between polypeptides induced by agents with different biologic properties, and identifications and characterization of Marek's disease induced polypeptides in transformed cells will be of particular interest. The methodology will include attempts to produce demylinating effects by passive transfer of Marek's disease derived serum and immunoglobulins or mononuclear cells, either separately or in combination. Direct inoculation of sciatic nerves in situ, and studies with myelinated cultures in vitro will be the experimental systems employed. In the studies of proteins, radiolabeled Marek's associated antigens will be immunoprecipitated with antibody from birds infected with the virus. Productively infected or transformed cell cultures will be the source of antigens, and these will be electrophoresed under denaturing conditions on polyacrylamide gels. These studies relate to our long-term objectives of understanding the pathogenesis of Marek's disease neuropathy, and the basis of the very different biologic properties exhibited by various isolates. Here, we are particularly interested in transforming agents. This investigation has general interest and significance because Marek's disease represents a readily exploitable natural model for defining the pathogenesis of demyelinating neuropathies (i.e. the Landry-Guillain-Barre syndrome) and Herpesvirus induced lymphoblastoid tumors.